Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy Alone or With Radiation Therapy in Treating Children With Kidney Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Completed	Under 16	NCI	COG-Q9401 NWTS-Q9401, CCG-4941, POG-9440, INT-0150, NWTS-5, NCT00002611, Q9401

Objectives

1. Increase survival rate of children with favorable histology (FH) Wilms' tumor and other childhood renal tumors.
2. Determine whether loss of heterozygosity for chromosome 16q or 1p in tumor tissue is associated with a poorer prognosis in children with FH Wilms' tumor.
3. Determine whether increased DNA content in tumor cells is associated with a poorer prognosis in children with FH Wilms' tumor.
4. Decrease the acute and long-term morbidity in children with Wilms' tumor by limiting initial therapy and consistently using the same regimen (protocol NWTS-5/R) for patients who relapse following initial treatment.
5. Improve overall and disease-free survival of patients with renal tumors of unfavorable histology, including Wilms' tumor with diffuse anaplasia and clear cell sarcoma of the kidney, using a new treatment regimen that includes etoposide (VP-16) and cyclophosphamide (CTX).
6. Improve overall and disease-free survival in patients with malignant rhabdoid tumor of the kidney using a new treatment regimen that includes carboplatin, VP-16, and CTX. (The rhabdoid tumor stratum closed to accrual effective 07/13/2001)
7. Provide data regarding loss of heterozygosity for chromosomes 11p15, 16q, and 1p, age at diagnosis, precursor lesions (perilobar, intralobar, nephroblastomatosis), bilaterality, and presence of congenital anomalies required for the completion of protocol A0026 (a case-control study of risk factors for Wilms' tumor).

Entry Criteria

Disease Characteristics:

• Histologically confirmed stage I-V kidney cancer of one of the following histologies:
  • Wilms' tumor, favorable histology
  • Wilms' tumor, focal or diffuse anaplastic
  • Clear cell sarcoma
  • Rhabdoid tumor

    (The rhabdoid tumor stratum closed to accrual effective 07/13/2001)




• Prior nephrectomy or biopsy required
  • Prior bilateral biopsy (preferably open) with bilateral staging and pathologic evaluation required for bilateral tumor



• Must begin study therapy within 5 days after nephrectomy (unless medically contraindicated)

Prior/Concurrent Therapy:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy

Surgery:

• See Disease Characteristics

Patient Characteristics:

Age:

• Under 16

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Other:

• Not pregnant
• Fertile patients must use effective contraception

Expected Enrollment

A total of 207 patients will be accrued for the treatment portion of this study. (The rhabdoid tumor stratum closed to accrual effective 07/13/2001.)

Outline

This is a multicenter study. Patients are assigned to one of nine strata based on tumor histology, stage, tumor weight, and age.

• Stratum 1 (stage I favorable histology (FH) Wilms' tumor, under 24 months of age, and tumor weight less than 550 g): After nephrectomy, patients receive regimen EE-4A comprising dactinomycin (DACT) IV weekly on weeks 0, 3, 6, 9, 12, 15, and 18 and vincristine (VCR) IV weekly on weeks 1-10, 12, 15, and 18.



• Stratum 2 (stage I FH Wilms' tumor and age 24 months and over or tumor weight at least 550 g; stage I focal anaplastic (FA) or diffuse anaplastic (DA) Wilms' tumor): Patients receive therapy as in stratum 1.



• Stratum 3 (stage II FH Wilms' tumor): Patients receive therapy as in stratum 1.



• Stratum 4 (stage III FH Wilms' tumor; stage II or III FA Wilms' tumor): After nephrectomy, patients receive regimen DD-4A comprising DACT IV weekly on weeks 0, 6, 12, 18, and 24; doxorubicin IV weekly on weeks 3, 9, 15, and 21; and VCR IV weekly on weeks 1-10, 12, 15, 18, 21, and 24. Patients also undergo abdominal radiotherapy.



• Stratum 5 (stage IV FH or FA Wilms' tumor): Patients receive chemotherapy as in stratum 4, abdominal radiotherapy, and whole lung radiotherapy (at the discretion of the investigator).



• Stratum 6 (stage V FH, FA, or DA Wilms' tumor ): After bilateral biopsy, patients with FH receive chemotherapy as in stratum 1 or 4. Patients with FA or DA receive chemotherapy as in stratum 7.



• Stratum 7 (stages I-IV clear cell sarcoma): After nephrectomy, patients receive VCR IV weekly on weeks 1, 2, 4-8, 10-13, 18, and 24; cyclophosphamide (CTX) IV over 1 hour on days 1-3 of weeks 6, 12, 18, and 24 and on days 1-5 of weeks 3, 9, 15, and 21; doxorubicin IV (beginning after CTX infusion) weekly on weeks 0, 6, 12, 18, and 24; and etoposide (VP-16) IV over 1 hour (beginning after CTX infusion) on days 1-5 of weeks 3, 9, 15, and 21. Filgrastim (G-CSF) is administered subcutaneously (SC) beginning 24 hours after completion of chemotherapy and continuing until blood counts recover. Patients also undergo abdominal radiotherapy and whole lung radiotherapy (if pulmonary metastases are present).



• Stratum 8 (stages II-IV DA Wilms' tumor): Patients receive treatment as in stratum 7.



• Stratum 9 (stages I-IV rhabdoid tumor): After nephrectomy, patients receive carboplatin IV on days 1-2 and VP-16 IV over 1 hour (beginning after carboplatin infusion) on days 1-3 of weeks 0, 3, 9, 12, 18, and 21 and CTX IV over 1 hour on days 1-5 of weeks 6, 15, and 24. G-CSF is administered as in stratum 7. Patients also undergo radiotherapy. (The rhabdoid tumor stratum closed to accrual effective 07/13/2001.)

After completion of chemotherapy, patients undergo second-look laparotomy and partial nephrectomy or wedge excision (if feasible). After second-look surgery, patients without persistent or residual disease resume chemotherapy.

Patients are followed every 3 months for 5 years, every 6 months for 2 years, and then annually for 3 years.

Fernandez CV, Anderson J, Breslow NE, et al.: Anthropomorphic measurements and event-free survival in patients with favorable histology Wilms tumor: a report from the Children's Oncology Group. Pediatr Blood Cancer 52 (2): 254-8, 2009.[PUBMED Abstract]

Huang CC, Gadd S, Breslow N, et al.: Predicting Relapse in Favorable Histology Wilms Tumor Using Gene Expression Analysis: A Report from the Renal Tumor Committee of the Children's Oncology Group. Clin Cancer Res : , 2009.[PUBMED Abstract]

Malogolowkin M, Cotton CA, Green DM, et al.: Treatment of Wilms tumor relapsing after initial treatment with vincristine, actinomycin D, and doxorubicin. A report from the National Wilms Tumor Study Group. Pediatr Blood Cancer 50 (2): 236-41, 2008.[PUBMED Abstract]

Dome JS, Cotton CA, Perlman EJ, et al.: Treatment of anaplastic histology Wilms' tumor: results from the fifth National Wilms' Tumor Study. J Clin Oncol 24 (15): 2352-8, 2006.[PUBMED Abstract]

Ehrlich PF, Hamilton TE, Grundy P, et al.: The value of surgery in directing therapy for patients with Wilms' tumor with pulmonary disease. A report from the National Wilms' Tumor Study Group (National Wilms' Tumor Study 5). J Pediatr Surg 41 (1): 162-7; discussion 162-7, 2006.[PUBMED Abstract]

Seibel NL, Sun J, Anderson JR, et al.: Outcome of clear cell sarcoma of the kidney (CCSK) treated on the National Wilms Tumor Study-5 (NWTS). [Abstract] J Clin Oncol 24 (Suppl 18): A-9000, 502s, 2006.

Dome JS, Bockhold CA, Li SM, et al.: High telomerase RNA expression level is an adverse prognostic factor for favorable-histology Wilms' tumor. J Clin Oncol 23 (36): 9138-45, 2005.[PUBMED Abstract]

Ehrlich PF, Ritchey ML, Hamilton TE, et al.: Quality assessment for Wilms' tumor: a report from the National Wilms' Tumor Study-5. J Pediatr Surg 40 (1): 208-12; discussion 212-3, 2005.[PUBMED Abstract]

Grundy PE, Breslow NE, Li S, et al.: Loss of heterozygosity for chromosomes 1p and 16q is an adverse prognostic factor in favorable-histology Wilms tumor: a report from the National Wilms Tumor Study Group. J Clin Oncol 23 (29): 7312-21, 2005.[PUBMED Abstract]

Miller MA, Karacay B, Breslow NE, et al.: Prognostic value of quantifying apoptosis factor expression in favorable histology wilms tumors. J Pediatr Hematol Oncol 27 (1): 11-4, 2005.[PUBMED Abstract]

Ritchey M, Daley S, Shamberger RC, et al.: Ureteral extension in Wilms' tumor: a report from the National Wilms' Tumor Study Group (NWTSG). J Pediatr Surg 43 (9): 1625-9, 2008.[PUBMED Abstract]

van den Heuvel-Eibrink MM, Grundy P, Graf N, et al.: Characteristics and survival of 750 children diagnosed with a renal tumor in the first seven months of life: A collaborative study by the SIOP/GPOH/SFOP, NWTSG, and UKCCSG Wilms tumor study groups. Pediatr Blood Cancer 50 (6): 1130-4, 2008.[PUBMED Abstract]

Breslow NE, Beckwith JB, Perlman EJ, et al.: Age distributions, birth weights, nephrogenic rests, and heterogeneity in the pathogenesis of Wilms tumor. Pediatr Blood Cancer 47 (3): 260-7, 2006.[PUBMED Abstract]

Kalapurakal JA, Nan B, Norkool P, et al.: Treatment outcomes in adults with favorable histologic type Wilms tumor-an update from the National Wilms Tumor Study Group. Int J Radiat Oncol Biol Phys 60 (5): 1379-84, 2004.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Daniel Green, MD, Protocol chair		Ph: 716-845-2334; 800-685-6825

Registry Information
Official Title		NATIONAL WILMS TUMOR STUDY-5 -- THERAPEUTIC TRIAL AND BIOLOGY STUDY
Trial Start Date		2002-05-31
Registered in ClinicalTrials.gov		NCT00002611
Date Submitted to PDQ		1995-07-05
Information Last Verified		2003-04-02
NCI Grant/Contract Number		CA13539, CA42326